Rheumatoid arthritis is a disease of unknown etiology. Considerable evidence indicates that the chronic articular and extra- articular inflammation in this disease results from immunological tissue injury. Recent observations indicate that antigen-antibody complexes exist in the synovial fluid and may well initiate the inflammation. However, the antigens involved have not been defined, but autologous gamma G-globulin is a possibility. The definition of antigens involved can lead to elucidation of the mechanisms of this disease and even discovery of the cause of rheumatoid arthritis. During the proposed project, immune complexes from synovial fluid will be purified by adsorption chromatography and immunochemical techniques will be used to identify the antigen(s) involved. Immunofluorescent microscopy will be used to search for antigens in the synovial tissue obtained from patients with rheumatoid arthritis during reconstructive surgery. Experimental animals will be used to study the fate of immune complexes in synovial space.